临床与病理杂志2025，Vol.45Issue(8)：951-966,16.DOI:10.11817/j.issn.2095-6959.2025.250413
基于棕榈酰化相关lncRNA构建胰腺癌的预后模型
Construction of a prognostic model for pancreatic adenocarcinoma based on palmitoylation-related lncRNA
摘要
Abstract
Objective:Pancreatic adenocarcinoma is a highly malignant gastrointestinal tumor with extremely poor prognosis.The lack of effective tools for early diagnosis and prognostic assessment is one of the main reasons for unsatisfactory treatment outcomes.Recent studies have shown that protein palmitoylation is closely related to tumor initiation and progression,while long non-coding RNA(lncRNA)play vital roles in tumorigenesis and prognosis.This study aims to identify palmitoylation-related lncRNA(PRlncRNA)and construct a prognostic model for pancreatic adenocarcinoma based on The Cancer Genome Atlas(TCGA)database. Methods:Transcriptomic data and clinical information of pancreatic cancer patients were obtained from the TCGA database.Pearson correlation analysis was used to identify PRlncRNA.Patients were randomly divided into a training and a validation set(1꞉1).Univariate Cox regression and least absolute shrinkage and selection operator(LASSO)regression analyses were conducted to identify survival-associated PRlncRNA,followed by multivariate Cox regression to determine independent prognostic factors and establish a prognostic risk model.Survival analysis and receiver operating characteristic(ROC)curves were used to assess the model's predictive performance,and area under the curve(AUC)values were calculated for 1-,3-,and 5-year overall survival(OS).A nomogram integrating risk scores and clinical factors was constructed,and calibration curves were used to evaluate its accuracy.Patients were classified into a high-risk group and a low-risk group based on the median risk score,and functional enrichment,immune infiltration,tumor mutation,and drug sensitivity analysis were performed between the 2 groups. Results:A total of 341 PRlncRNA were identified,and 7(AC005332.6,AC007728.2,AC011498.6,AC025165.1,LINC00857,LINC02245,and PTPRN2-AS1)were determined as independent prognostic markers to construct the risk model.Survival analysis revealed that higher risk scores were associated with increased mortality and significantly shorter overall survival.The AUC values for 1-,3-,and 5-year OS were 0.744,0.790,and 0.835,respectively.The calibration curves indicate strong agreement between predicted and observed outcomes.Functional enrichment analysis suggested that differentially expressed genes were mainly involved in tumor-related signaling pathways and immune regulation.Immune infiltration analysis showed significant differences in immune cell infiltration and immune functions between the high-risk group and the low-risk group(P<0.05).Low-risk patients exhibited higher expression of immune checkpoint genes(all P<0.05),while high-risk patients had higher tumor mutation burden(TMB)(P<0.05).Drug sensitivity analysis indicated that the low-risk group showed significantly lower half-maximal inhibitory concentration(IC50)for 9 anti-tumor drugs(Alisertib,AT13148,AZD1208,BMS-754807,Cediranib,Foretinib,I-BET-762,JQ1,and MK-2206)(all P<0.05). Conclusion:The prognostic model based on PRlncRNA expression can effectively predict survival outcomes in pancreatic adenocarcinoma patients and may serve as a valuable reference for clinical decision-making and individualized treatment strategies.关键词
棕榈酰化/长链非编码RNA/胰腺癌/预后/免疫治疗Key words
palmitoylation/long non-coding RNA/pancreatic adenocarcinoma/prognosis/immunotherapy引用本文复制引用
傅旺旺,龚晓文,阚卫军,张晓栋,张永平..基于棕榈酰化相关lncRNA构建胰腺癌的预后模型[J].临床与病理杂志,2025,45(8):951-966,16.基金项目
山西省卫生健康委员会科研课题(2019031).This work was supported by the Scientific Research Project of Health Commission of Shanxi Province,China(2019031). （2019031）
